Transcriptional programs regulated by MYCN in liver tumorigenesis
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ABSTRACT:
PROVIDER: PRJNA1291076 | ENA |
REPOSITORIES: ENA
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Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, often diagnosed at advanced stages and characterized by high recurrence rates. While chronic liver inflammation and metabolic dysfunction are recognized contributors to tumorigenesis, the molecular mechanisms linking early microenvironmental stress to malignant transformation remain poorly understood. MYCN, a proto-oncogenic transcription factor, has emerged as a potential biomarker of cancer stemness, yet its functional role in hepatocarcinogenesis is unclear. Here, we applied CUT&RUN-seq analysis and integrated the data with RNA-seq to investigate the direct transcriptional impact of MYCN in liver tumorigenesis. Transcriptomic profiling revealed that MYCN-driven tumors exhibit features of human HCC subtypes enriched in stress-adaptive gene programs. We found genes with upstream MYCN binding showed significantly greater expression changes between tumor and non-tumor samples, suggesting that MYCN binding in promoter-proximal regions has a stronger influence on transcriptional regulation. Pathway analysis revealed significant enrichment in pathways related to cytoskeletal organization, cell motility, and membrane dynamics, all of which are central to intercellular interactions and tumor microenvironment remodeling, indicating that MYCN regulates pathways contributing to tumor microenvironment remodeling and cellular interactions.
2025-07-19 | GSE302484 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, often diagnosed at advanced stages and characterized by high recurrence rates. While chronic liver inflammation and metabolic dysfunction are recognized contributors to tumorigenesis, the molecular mechanisms linking early microenvironmental stress to malignant transformation remain poorly understood. MYCN, a proto-oncogenic transcription factor, has emerged as a potential biomarker of cancer stemness, yet its functional role in hepatocarcinogenesis is unclear. Here, we elucidate the oncogenic role of MYCN and its dynamic regulation during metabolic liver tumorigenesis. Transcriptomic profiling revealed that MYCN-driven tumors exhibit features of human HCC subtypes enriched in stress-adaptive transcriptional programs. Time-resolved spatial transcriptomics further uncovered a MYCN-enriched niche characterized by epithelial–mesenchymal transition (EMT) and Wnt/β-catenin signaling, which expanded during tumor progression and was spatially proximate to transformed malignant cells.
2025-07-30 | GSE302815 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, often diagnosed at advanced stages and characterized by high recurrence rates. While chronic liver inflammation and metabolic dysfunction are recognized contributors to tumorigenesis, the molecular mechanisms linking early microenvironmental stress to malignant transformation remain poorly understood. MYCN, a proto-oncogenic transcription factor, has emerged as a potential biomarker of cancer stemness, yet its functional role in hepatocarcinogenesis is unclear. Here, we elucidate the oncogenic role of MYCN and its dynamic regulation during metabolic liver tumorigenesis.Using a transposon system in mice and the human hepatocyte cell line Hc, we demonstrate that MYCN overexpression functionally promotes liver tumorigenesis and hepatocyte transformation. Transcriptomic profiling of MYCN-driven tumors revealed molecular features resembling human HCC subtypes enriched in stress-adaptive gene programs, highlighting MYCN's role in shaping tumor-promoting transcriptional landscapes.
2025-07-16 | GSE302338 | GEO
Project description:Spatial transcriptional features of MYCN niche in liver tumorigenesis.
| PRJNA1292214 | ENA
Project description:MYCN is a common oncogenic alteration in tumors, representing one of the high-risk molecular subtypes of tumors. However, the functional role of MYCN in tumorigenesis remains to be elucidated. Here, we report that MYCN binds to the UBE2C promoter and upregulates its transcription, accelerating the progression of neuroectodermal tumor. The proteomic analysis of UBE2C-interacting proteins revealed TFRC, a well-known tumor suppressor, is a novel ubiquitin target of UBE2C. Subsequently, immunoprecipitation assay demonstrates UBE2C downregulate TFRC expression via ubiquitinoylation in neuroectodermal tumor. Suppression of UBE2C in tumor cells induced ferroptosis and increased sensitivity to the ferroptosis inducer erastin. Taken together, our findings reveal a novel MYCN-UBE2C-TFRC-ferroptosis regulatory cascade in controlling MYCN activation cell proliferation and tumor growth, pinpointing an unprecedented mechanism of MYCN-mediated evasion of ferroptosis escape in tumor. This study provides useful insights into the theoretical underpinning for therapy of MYCN activation tumors.
| PXD053344 |
Project description:Neuroblastoma is a pediatric cancer of the sympathetic nervous system. MYCN amplification is a key indicator of poor prognosis for the disease, however, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. Based on a Bayesian learning network model in which we compared pre-tumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA-mRNA interaction network. Among the miRNA-mRNA interactions operating during human neuroblastoma tumorigenesis, we identified that miR-204 is a tumor suppressor miRNA that inhibits a subnetwork of oncogenes strongly associated with MYCN-amplified neuroblastoma and poor patient outcome. Accordingly, we found that MYCN was bound to the miR-204 promoter and repressed miR-204 transcription, while in contrast, miR-204 directly bound MYCN mRNA and repressed MYCN expression. In support of a tumor suppressor role, miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis.
2018-06-01 | GSE100658 | GEO
Project description:Changes in epigenetic regulation are believed to be a major contributing factor to neuroblastoma development. Using a large-scale in vivo mutagenesis screen in Th-MYCN transgenic mice, we identified a single point mutation in the transcriptional corepressor Runx1t1, that can block N-myc-driven neuroblastoma tumorigenesis. The loss of function mutation disrupts a highly conserved zinc finger domain (NHR4) within Runx1t1. Crossing an independent Runx1t1 knockout model with Th-MYCN mice, demonstrated that Runx1t1 haploinsufficiency is enough to prevent neuroblastoma development and reverse ganglia hyperplasia. Silencing RUNX1T1 in human neuroblastoma cells resulted in decreased colony formation in vitro, and significant inhibition of tumor growth in vivo. Our results show that RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex that regulates the epigenomic landscape and chromatin accessibility, to control neuron-specific pathway genes and maintain an undifferentiated state. Runx1t1 thus represents an entirely novel and highly promising target not previously described in neuroblastoma.
2024-08-10 | PXD050375 | Pride
Project description:This study investigated the transcriptional changes associated with Mycn-induced adrenal tumor development in mice. RNA sequencing was performed using luciferase-expressing adrenal medulla samples and Mycn-induced adrenal tumors collected at different times after transgene induction. The dataset was generated to characterize early and advanced transcriptional states during Mycn-driven adrenal tumorigenesis.
2026-08-24 | GSE339002 | GEO
Project description:This study investigated the transcriptional responses induced by c-Myc and Mycn in primary mouse hepatocytes. Primary hepatocytes expressing luciferase, Mycn, or c-Myc were collected at 12 h, day 3, day 6, and day 12 after transgene induction and analyzed by RNA sequencing. The dataset was generated to compare the temporal transcriptional programs induced by Mycn and c-Myc during hepatocyte transformation.
2026-08-24 | GSE339001 | GEO